Transporters of Emerging Importance in Drug Development: Beyond the Guidance Documents
Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting
In October, 2017, the US FDA revised and split its 2012 draft guidance for industry on in vitro drug-drug interaction (DDI) studies, into one document for in vitro DDI studies, and another for clinical DDI studies. For investigation of the transporter inhibition or substrate potential of drug candidates, the FDA updated the prior in vitro list (i.e., P-gp, BCRP, OATP1B1 & 3, OAT1 & 3, and OCT2) to include MATE1 and MATE2-K. Notably absent from this list was OCT1, which is a highly polymorphic hepatic uptake transporter, included in the European Medicines Agency (EMA) Final DDI Guideline from 2013.
In 2018 the International Transporter Consortium published a paper recommending prospective evaluation of OCT1. Other transporters covered by the ITC, including OATP2B1 and OAT2, along with the evidence for their emerging importance will also be highlighted. Finally, consideration of other transporters important for drug distribution during atypical routes of administration will be discussed (e.g., nasal and ophthalmic).
Key concepts discussed in this webinar will include:
- 2017 FDA guidance update
- In vitro transporter additions and eliminations in updated guidance
- OCT1 evaluation in FDA versus EMA official documents
- Impacts of polymorphisms
- 2018 ITC paper discussing OCT1
- Other important transporters covered by ITC paper
- Extended Clearance Classification System (ECCS) prediction of rate-determining step in Absorption, Distribution, Clearance & Elimination (ADCE)
- Atypical routes of administration